Abstract 6261A: Chinese medicinal herbs Scutellaria barbata and Oldenlandia diffusa modulate apoptosis via induction of pro-apoptotic and anti-apoptotic proteins in MDA-MB-157 and 93B breast cancer cells

Abstract

Abstract Scutellaria barbata (SB) and Oldenlandia diffusa (OD) have been used in Traditional Chinese Medicine for treating colon cancer, glioblastoma, and ovarian cancer liver, lung, and rectal cancers. These two herbs are included in most of the herbal cancer treatment formulas in China and Taiwan hospitals. We previously demonstrated that aqueous extracts of SB and OD inhibited mutagenesis, DNA binding, and metabolism of aflatoxin B1 and benzo[a]pyrene in carcinogenesis. In studies by Hugo (2006) and Perez (2010), the efficacy of BZL 101 (an extract of SB) has been demonstrated in preliminary Phase Ia and Ib clinical trials in metastatic breast cancer patients. It is also shown to induce an S phase arrest of the cell cycle by affecting the Cycline A2 and CDK2 expression in estrogen-sensitive MCF7 and estrogen insensitive MDA-MB-231 breast cancer cells. MeOH and BuOH extract of OD have been illustrated to reduce MCF7 invasion via the inhibition of MMP-9 and ICAM-1 apoptotic proteins expression. Ursolic acid of OD could inhibit breast cancer metastasis by suppressing glycolytic metabolism through activating SP1/Caveolin-1 signaling. In this study, the effectiveness of aqueous extract of SB and OD in the modulation of apoptosis of breast cancer cell lines MDA-MB-157 and 93B (a drug-resistant APC-mutant of it) were investigated. Assessments were performed using green/red/blue fluorescent Apoptosis/Necrosis Detection Test and the Human Apoptosis Antibody Array - Membrane [43 Targets] Test (Abcam). Our fluorescent apoptosis data showed that 3-hours treatment with 2.5 mg aqueous extract of SB induced a statistically significant percentage of apoptosis in MDA-MB-157 (46.5 ± 7.5% > 16%± 1.0%, p < 0.05) and 93B (46.5 ± 7.5% > 16%± 1.0%, p < 0.05) as compared to the negative control. Similar results were obtained with the OD treatment. From the antibody array-membrane experiments, modulation of various apoptosis markers by SB such as the pro-apoptotic proteins BID and BIM (p=0.019; p=0.007) in MDA-MB-157 and Bad (p=0.002), Bax (p=0.020), BID (p=0.001), p27 (p=0.004), p53 (p=0.022) in 93B as compared to the negative controls; and anti-apoptotic markers BcL-2, FasL, IGF-I, and p21 were also observed. OD treatment also induced similar significant production of these two types of proteins. These results suggest that SB and OD contain phytochemicals that induce apoptosis in MDA-MB-157 and 93B via the modulation of these pro-apoptotic and anti-apoptotic proteins. Citation Format: MinSeo Kang, Nathaly Manrique, Rekha Issac, Sarah Wolf, Jasmine Cha, SungBeen Han, Hugo Jie Qin, Lun Kim, Padma P. Uppala, Brian Yuen Yau Wong. Chinese medicinal herbs Scutellaria barbata and Oldenlandia diffusa modulate apoptosis via induction of pro-apoptotic and anti-apoptotic proteins in MDA-MB-157 and 93B breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6261A.