Abstract
Plantaginaceae, a popular traditional Chinese medicine, has long been used for treating various diseases from common cold to cancer. Linalool is one of the biologically active compounds that can be isolated from Plantaginaceae. Most of the commonly used cytotoxic anticancer drugs have been shown to induce apoptosis in susceptible tumor cells. However, the signaling pathway for apoptosis remains undefined. In this study, the cytotoxic effect of linalool on human cancer cell lines was investigated. Water-soluble tetrazolium salts (WST-1) based colorimetric cellular cytotoxicity assay, was used to test the cytotoxic ability of linalool against U937 and HeLa cells, and flow cytometry (FCM) and genechip analysis were used to investigate the possible mechanism of apoptosis. These results demonstrated that linalool exhibited a good cytotoxic effect on U937 and HeLa cells, with the IC50 value of 2.59 and 11.02 μM, respectively, compared with 5-FU with values of 4.86 and 12.31 μM, respectively. After treating U937 cells with linalool for 6 h, we found an increased sub-G1 peak and a dose-dependent phenomenon, whereby these cells were arrested at the G0/G1 phase. Furthermore, by using genechip analysis, we observed that linalool can promote p53, p21, p27, p16, and p18 gene expression. Therefore, this study verified that linalool can arrest the cell cycle of U937 cells at the G0/G1 phase and can arrest the cell cycle of HeLa cells at the G2/M phase. Its mechanism facilitates the expression of the cyclin-dependent kinases inhibitors (CDKIs) p53, p21, p27, p16, and p18, as well as the non-expression of cyclin-dependent kinases (CDKs) activity.
Highlights
According to a statistical report by the World Health Organization, cervical cancer is the second most common cancer in women
The results indicated that linalool reduces the expression levels of Bcl-2 and Bcl-XL genes and enhances the drug‘s toxicity on U937 and HeLa cells
U937 and HeLa cells show that the overexpression of p53, p21, p27, p16, and p18 genes causing the cell cycle to arrest at the G0/G1 and G2/M phases, respectively
Summary
According to a statistical report by the World Health Organization, cervical cancer is the second most common cancer in women. More than 250,000 women are estimated to die annually from cervical cancer [1]. Previous studies have demonstratteedd tthhee cyyttoottooxxiicc eeffffeecctt ooff PPllaannttaaggiinnaacceeaaee,, a type of traditional medicinal plant [16–20]. Linalool is a member of the monoterpenoids family of compounds that come from medicinal plants aanndd aarree rreeccooggnniizzeedd aass aa ggrroouupp ooff ppootteennttiiaall cchheemmoopprreevveennttiivvee ccoommppoouunnddss. LLiinnaallooool is oonnee ssuucchh ccoommppoouunndd tthhaatt hhaass bbeeeenn rreeppoorrtteedd ttoo iinnhhiibbiitt tthhee ggrroowwtthh ooff vvaarriioouuss hhuummaann ccaanncceerr cceellllss bbyy ccaauussiinngg aappooppttoottiicc cceellll ddeeaatthh [[2211––2233]]. HHoowweevveerr,, ddeessppiittee tthhee aaccccuummuullaattiioonn ooff ddaattaa,, tthhee mmoolleeccuullaarr mmeecchhaanniissmm bbyy wwhhiicchh lliinnaallooooll aaccttssaaggaaininssttleleuukkeemmiaiaaannddcecrevrivciaclacl acnacnecrecreclelslliss isstislltiullnuexnpexloprleodre. DIn. tIhnisthstius dsytu, dwye, wineveinstviegsattiegathtee tchyetoctyotxoitcoxeficfeecftfeocftlionfallionoalloaoglaaingsatinUs9t3U79a3n7daHndeLHaecLeallsc.eTllhs.roTuhgrhouflgohwflcoywtocmyetotrmyeatnryd agnednegcehnipechanipalaynseasly, swese, wweerwe earbelaebtloe tdoedteertmerimneinheohwowlinlianlaoloololsusupppprersessessesththee rreegguullaattiioonn ooff bbootthh lleeuukkeemmiiaa aanndd cceerrvviiccaall ccaanncceerr cceellll ccyycclleess HHoowweevveerr,, ddeessppiittee tthhee aaccccuummuullaattiioonn ooff ddaattaa,, tthhee mmoolleeccuullaarr mmeecchhaanniissmm bbyy wwhhiicchh lliinnaallooooll aaccttssaaggaaininssttleleuukkeemmiaiaaannddcecrevrivciaclacl acnacnecrecreclelslliss isstislltiullnuexnpexloprleodre. dIn. tIhnisthstius dsytu, dwye, wineveinstviegsattiegathtee tchyetoctyotxoitcoxeficfeecftfeocftlionfallionoalloaoglaaingsatinUs9t3U79a3n7daHndeLHaecLeallsc.eTllhs.roTuhgrhouflgohwflcoywtocmyetotrmyeatnryd agnednegcehnipechanipalaynseasly, swese, wweerwe earbelaebtloe tdoedteertmerimneinheohwowlinlianlaoloololsusupppprersessessesththee rreegguullaattiioonn ooff bbootthh lleeuukkeemmiiaa aanndd cceerrvviiccaall ccaanncceerr cceellll ccyycclleess
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