A possible chemotherapeutic response by paclitaxel and other antineoplastic agents in treatment of choriocarcinoma in vitro

Abstract

To the Editors:I have read with interest the article by Marth et al. (Marth C, Lang T, Widschwendter M, Müller-Holzner E, Daxenbichler G. Effects of Taxol on choriocarcinoma cells. Am J Obstet Gynecol 1995;173:1835-42). The authors discussed the biologic properties of paclitaxel (Taxol) as an antineoplastic agent in two choriocarcinoma cell lines, JAR and BeWo. They found that Taxol promoted differentiation of these cells. They concluded that Taxol is a highly effective agent when combined with either etoposide or methotrexate.I would like to raise an issue to be incorporated into the current knowledge of Taxol and its chemotherapeutic effect regarding Taxol and other microtubule active agents: vinblastine and nocodazole. Taxol induces tumor suppressor gene P53 in a dose-dependent manner. P53 induction leads to an increase of cells with a 2N deoxyribonucleic acid content based on the block in G1. One possibility is that there is a transient induction of a G1 block. However, cells treated with drug for 6 hours show a decrease in the fraction of cells in G2, indicating that a G1 block is not being affected. A possible explanation is that the P53 is only induced by these agents when cells are past the point in G1 at which cells could be stopped by the check point (i.e., these agents may only induce P53 in G2).1Tisbier RB Lamppu DM Parks S Price BD Microtubule-active drugs Taxol, vinblastine, and nocodazole increase the levels of transcriptionally active p53.Cancer Res. 1995; 55: 6021-6025PubMed Google ScholarSecond, the authors concluded on the basis of their experiment that Taxol is a highly effective antineoplastic agent in choriocarcinoma cells. I would like to draw the authors' attention to the fact that to obtain a chemosensitivity profile cells of the four primary types of gestational trophoblastic disease (complete hydatidiform mole, partial hydatidiform mole, gestational choriocarcinoma, and placental site trophoblastic tumor) must be tested. It has been shown that the adenosine triphosphate cell viability assay in fresh gestational trophoblastic neoplasms invasive mole and choriocarcinoma were chemosensitive; on the other hand, the placental site was revealed to be chemoresistant.2Koechli OR Schaer GN Sevin BU et al.In vitro chemosensitivity of paclitaxel and other chemotherapeutic agents in malignant gestational trophoblastic neoplasms.Anti Cancer Drug. 1995; 1: 94-100Crossref Scopus (13) Google ScholarThird, the authors did not take in consideration the cytotoxic activity of human tumor necrosis factor-α (TNF-α) in their experiment. It is well recognized that the cytotoxic activity of human TNF-α and Taxol is enhanced when combined with certain chemotherapeutic agents. It has been shown that the combination of low concentrations of human TNF-α with Taxol could increase the cytotoxic activity of Taxol in SKOV3 cells. Furthermore, a 4-hour pretreatment with Taxol before adding human TNF-α to the culture has shown a significant increase in cytotoxicty activity. This increase was not observed at the same level in SKOV3 cells pretreated with human TNF-α.3Berkova N Page M Addition of hTNF alpha potentiates cytotoxicity of Taxol in human ovarian cancer lines.Anti Cancer-Res. 1995 May-June; 15: 863-866PubMed Google ScholarFinally, in this experiment the authors did not investigate in vitro the activity of various formulations of paclitaxel and its solvent in tumor samples from the tumor cell line. It was observed that was a decrease in cell survival after only 3 hours of incubation in Taxol or Cremophor EL (ethanol-formulated paclitaxel). This is reminiscent of the rapid cytotoxic effect of fatty acids, indicating related mechanisms of action. The possibility of a unique cytotoxic effect of CEL in Taxol would also explain the poor cross-resistance to the standard drugs.4Nygren P Csoka K Jonsson B et al.The cytotoxic activity of Taxol in primary cultures of tumor cells from patient is partly mediated by Cremophor EL.Br J Cancer. 1995; 71: 478-481Crossref PubMed Scopus (49) Google Scholar Overall, the authors' conclusion that Taxol is a highly effective antineoplastic agent in choriocarcinoma cells is unfounded because the different variables must be tested with the drug. A large study comprising fresh malignant gestational trophoblastic neoplastic tumors that can be differentiated on the basis of histopathologic and cytogenic finding, clinical features, and location of the tumor to determine more accurately in vitro chemosensitivity would perhaps be more enlightening.6/8/75842 To the Editors:I have read with interest the article by Marth et al. (Marth C, Lang T, Widschwendter M, Müller-Holzner E, Daxenbichler G. Effects of Taxol on choriocarcinoma cells. Am J Obstet Gynecol 1995;173:1835-42). The authors discussed the biologic properties of paclitaxel (Taxol) as an antineoplastic agent in two choriocarcinoma cell lines, JAR and BeWo. They found that Taxol promoted differentiation of these cells. They concluded that Taxol is a highly effective agent when combined with either etoposide or methotrexate.I would like to raise an issue to be incorporated into the current knowledge of Taxol and its chemotherapeutic effect regarding Taxol and other microtubule active agents: vinblastine and nocodazole. Taxol induces tumor suppressor gene P53 in a dose-dependent manner. P53 induction leads to an increase of cells with a 2N deoxyribonucleic acid content based on the block in G1. One possibility is that there is a transient induction of a G1 block. However, cells treated with drug for 6 hours show a decrease in the fraction of cells in G2, indicating that a G1 block is not being affected. A possible explanation is that the P53 is only induced by these agents when cells are past the point in G1 at which cells could be stopped by the check point (i.e., these agents may only induce P53 in G2).1Tisbier RB Lamppu DM Parks S Price BD Microtubule-active drugs Taxol, vinblastine, and nocodazole increase the levels of transcriptionally active p53.Cancer Res. 1995; 55: 6021-6025PubMed Google ScholarSecond, the authors concluded on the basis of their experiment that Taxol is a highly effective antineoplastic agent in choriocarcinoma cells. I would like to draw the authors' attention to the fact that to obtain a chemosensitivity profile cells of the four primary types of gestational trophoblastic disease (complete hydatidiform mole, partial hydatidiform mole, gestational choriocarcinoma, and placental site trophoblastic tumor) must be tested. It has been shown that the adenosine triphosphate cell viability assay in fresh gestational trophoblastic neoplasms invasive mole and choriocarcinoma were chemosensitive; on the other hand, the placental site was revealed to be chemoresistant.2Koechli OR Schaer GN Sevin BU et al.In vitro chemosensitivity of paclitaxel and other chemotherapeutic agents in malignant gestational trophoblastic neoplasms.Anti Cancer Drug. 1995; 1: 94-100Crossref Scopus (13) Google ScholarThird, the authors did not take in consideration the cytotoxic activity of human tumor necrosis factor-α (TNF-α) in their experiment. It is well recognized that the cytotoxic activity of human TNF-α and Taxol is enhanced when combined with certain chemotherapeutic agents. It has been shown that the combination of low concentrations of human TNF-α with Taxol could increase the cytotoxic activity of Taxol in SKOV3 cells. Furthermore, a 4-hour pretreatment with Taxol before adding human TNF-α to the culture has shown a significant increase in cytotoxicty activity. This increase was not observed at the same level in SKOV3 cells pretreated with human TNF-α.3Berkova N Page M Addition of hTNF alpha potentiates cytotoxicity of Taxol in human ovarian cancer lines.Anti Cancer-Res. 1995 May-June; 15: 863-866PubMed Google ScholarFinally, in this experiment the authors did not investigate in vitro the activity of various formulations of paclitaxel and its solvent in tumor samples from the tumor cell line. It was observed that was a decrease in cell survival after only 3 hours of incubation in Taxol or Cremophor EL (ethanol-formulated paclitaxel). This is reminiscent of the rapid cytotoxic effect of fatty acids, indicating related mechanisms of action. The possibility of a unique cytotoxic effect of CEL in Taxol would also explain the poor cross-resistance to the standard drugs.4Nygren P Csoka K Jonsson B et al.The cytotoxic activity of Taxol in primary cultures of tumor cells from patient is partly mediated by Cremophor EL.Br J Cancer. 1995; 71: 478-481Crossref PubMed Scopus (49) Google Scholar Overall, the authors' conclusion that Taxol is a highly effective antineoplastic agent in choriocarcinoma cells is unfounded because the different variables must be tested with the drug. A large study comprising fresh malignant gestational trophoblastic neoplastic tumors that can be differentiated on the basis of histopathologic and cytogenic finding, clinical features, and location of the tumor to determine more accurately in vitro chemosensitivity would perhaps be more enlightening. I have read with interest the article by Marth et al. (Marth C, Lang T, Widschwendter M, Müller-Holzner E, Daxenbichler G. Effects of Taxol on choriocarcinoma cells. Am J Obstet Gynecol 1995;173:1835-42). The authors discussed the biologic properties of paclitaxel (Taxol) as an antineoplastic agent in two choriocarcinoma cell lines, JAR and BeWo. They found that Taxol promoted differentiation of these cells. They concluded that Taxol is a highly effective agent when combined with either etoposide or methotrexate. I would like to raise an issue to be incorporated into the current knowledge of Taxol and its chemotherapeutic effect regarding Taxol and other microtubule active agents: vinblastine and nocodazole. Taxol induces tumor suppressor gene P53 in a dose-dependent manner. P53 induction leads to an increase of cells with a 2N deoxyribonucleic acid content based on the block in G1. One possibility is that there is a transient induction of a G1 block. However, cells treated with drug for 6 hours show a decrease in the fraction of cells in G2, indicating that a G1 block is not being affected. A possible explanation is that the P53 is only induced by these agents when cells are past the point in G1 at which cells could be stopped by the check point (i.e., these agents may only induce P53 in G2).1Tisbier RB Lamppu DM Parks S Price BD Microtubule-active drugs Taxol, vinblastine, and nocodazole increase the levels of transcriptionally active p53.Cancer Res. 1995; 55: 6021-6025PubMed Google Scholar Second, the authors concluded on the basis of their experiment that Taxol is a highly effective antineoplastic agent in choriocarcinoma cells. I would like to draw the authors' attention to the fact that to obtain a chemosensitivity profile cells of the four primary types of gestational trophoblastic disease (complete hydatidiform mole, partial hydatidiform mole, gestational choriocarcinoma, and placental site trophoblastic tumor) must be tested. It has been shown that the adenosine triphosphate cell viability assay in fresh gestational trophoblastic neoplasms invasive mole and choriocarcinoma were chemosensitive; on the other hand, the placental site was revealed to be chemoresistant.2Koechli OR Schaer GN Sevin BU et al.In vitro chemosensitivity of paclitaxel and other chemotherapeutic agents in malignant gestational trophoblastic neoplasms.Anti Cancer Drug. 1995; 1: 94-100Crossref Scopus (13) Google Scholar Third, the authors did not take in consideration the cytotoxic activity of human tumor necrosis factor-α (TNF-α) in their experiment. It is well recognized that the cytotoxic activity of human TNF-α and Taxol is enhanced when combined with certain chemotherapeutic agents. It has been shown that the combination of low concentrations of human TNF-α with Taxol could increase the cytotoxic activity of Taxol in SKOV3 cells. Furthermore, a 4-hour pretreatment with Taxol before adding human TNF-α to the culture has shown a significant increase in cytotoxicty activity. This increase was not observed at the same level in SKOV3 cells pretreated with human TNF-α.3Berkova N Page M Addition of hTNF alpha potentiates cytotoxicity of Taxol in human ovarian cancer lines.Anti Cancer-Res. 1995 May-June; 15: 863-866PubMed Google Scholar Finally, in this experiment the authors did not investigate in vitro the activity of various formulations of paclitaxel and its solvent in tumor samples from the tumor cell line. It was observed that was a decrease in cell survival after only 3 hours of incubation in Taxol or Cremophor EL (ethanol-formulated paclitaxel). This is reminiscent of the rapid cytotoxic effect of fatty acids, indicating related mechanisms of action. The possibility of a unique cytotoxic effect of CEL in Taxol would also explain the poor cross-resistance to the standard drugs.4Nygren P Csoka K Jonsson B et al.The cytotoxic activity of Taxol in primary cultures of tumor cells from patient is partly mediated by Cremophor EL.Br J Cancer. 1995; 71: 478-481Crossref PubMed Scopus (49) Google Scholar Overall, the authors' conclusion that Taxol is a highly effective antineoplastic agent in choriocarcinoma cells is unfounded because the different variables must be tested with the drug. A large study comprising fresh malignant gestational trophoblastic neoplastic tumors that can be differentiated on the basis of histopathologic and cytogenic finding, clinical features, and location of the tumor to determine more accurately in vitro chemosensitivity would perhaps be more enlightening. 6/8/75842