Apoptotic exert protective effects against various types

Apoptotic study

Compound 6 (3,6,7-trihydroxy-2-(3-methoxyphenyl)-4H-chromen-4-one) possessing good cytotoxic activity against the breast and lung cancer cell line belongs to the group of flavonoids.

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Flavonoids are part of the polyphenol class of phytonutrients. Research on flavonoids had shown major developments in anticancer drug discoveries with the potential to destroy cancer cells through apoptotic induction 28. Flavonoids exert protective effects against various types of tumors including oral and pharyngeal, gastric, pancreatic, colorectal, hepatic, prostate, ovarian, endometrial, breast, and lung cancers 29.

As reported by Riaz et al. from the various literatures various flavonoids which showed anticancer activity on different human cancers include flavanones, daidzein, genistein, quercetin, luteolin which are effective against breast cancer, flavones-quercetin have also been proved to be potent against human lung cancer, catechin, epicatechin, quercetin, kaempferol, luteolin, genistein, apigenin, myricetin, silymarin possess significant effect against human prostate cancer 30. Sathish et.al have reported the isolation of (3,6,7-trihydroxy-2-(3-methoxyphenyl)-4H-chromen-4-one) from the ethanol extract of C.phlomidis root and has evaluated the cytotoxic activity against Hela cell lines and the IC50 value was found to be 209.4 ?g/ml 31.

The molecular mechanism of flavonoids in cancer prevention remains unclear; some studies proposed that flavonoids interact with different types of genes and enzymes. Some mechanisms of action of flavonoids have been identified, such as inactivation of carcinogens, anti-proliferation, cell cycle inhibition, apoptotic induction, inhibition of angiogenesis, antioxidants, or the combination of such mechanisms 32.

To find out whether the cytotoxic activity of the isolated chemical constituents was due to apoptosis, MCF-7 cells were treated with the compounds 6 and 9 at 2 × IC50 for 24 hours. In the control or untreated MCF-7 cells, there was no prominent morphological or nuclear changes, the stained nuclei were rounded and evenly stained with DAPI. The cancer cells treated with the sample compounds 6 and 9 showed different stained DNA nuclei compared to the control group, by the presence of condensed chromatin and apoptotic bodies that are the characteristic of the early and late stages of apoptosis. Compound 6 and 9 induced 74.50 ± 6.03% and 85.48 ± 2.95% apoptosis in MCF-7 cells. Determination of apoptosis was further carried out by evaluating the DNA laddering as a result of DNA fragmentation, which is typical of the late stage of apoptosis. DNA laddering was observed in the MCF-7 cells treated with the compounds 6 and 9.