Apoptosis induction on colon cancer cells from the Calotropis gigantea stem bark extract

Abstract

The drawbacks of chemotherapeutic agents in colorectal cancer cells (CRC) are systemic side effects, and drug resistance which generates limitations during the therapy. Natural products are being greatly focused on in the hope that they will be able to replace the medications. The anticancer effects of different parts of the Calotropis gigantea (C. gigantea) have been reported, however, the inhibitory effects on cancer cell proliferation from its stem bark extracts in CRC have not yet been examined. This study investigated the anticancer effects of the four fractions from the stem bark extracts of C. gigantea, both singularly and combined with 5-fluorouracil (5-FU). Dry powder from the C. gigantea bark was extracted using 95% ethanol to obtain the ethanolic crude extract (CGEtOH), then dichloromethane (CGDCM) was added to the extract, which created ethyl acetate (CGEtOAC), and water (CGW) layers. The cytotoxic effect from one CGDCM fraction showed the highest potency in both HCT116 and HT-29 cells, while the HCT116 cells combined with 5-FU demonstrated a more significant effect. The resistance of normal fibroblast HFF-1 cells to the treatment demonstrated a safety usage for normal cells, while the combination significantly enhanced apoptosis via the mitochondrial-dependent pathway. Reducing the ATP production and increasing ROS generation after treatment with the combination caused apoptotic induction. Our results suggest that DCM extracts from the stem bark of the C. gigantea demonstrated promising anti-cancer activities, and potential effects to facilitate apoptotic induction with 5-fluorouracil in the treatment of CRC with reduced toxicity to normal human cells.

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