Differential Cytotoxic Potential of Acridocarpus orientalis Leaf and Stem Extracts with the Ability to Induce Multiple Cell Death Pathways

Abstract

This study systematically analyzed the anticancer potential of Acridocarpus orientalis (AO), a traditional medicinal plant of the Arabian Peninsula/East Africa known for its anti-inflammatory and pain relief properties. Tests of serial organic fractions from methanolic extracts of its leaves and stems revealed that only some fractions showed anti-proliferative potential with the dichloromethane fraction from leaves (AOD (L)) showing the most cytotoxic effect against both breast (MCF-7 and MDA-MB-231) and cervical (HeLa) cancer cell lines. The n-butanol fraction from the stems (AOB (S)), on the other hand, was more effective against cervical cancer cells and did not harm the normal cells. Further characterization of the mode of cell killing revealed that AOD (L) depended more on non-apoptotic pathways for its cytotoxicity in breast cancer cells, while it could activate some apoptosis and necroptosis in HeLa cells. The AOB (S) fraction could primarily activate apoptosis and some necroptosis in HeLa cells. Both fractions perturbed autophagy, but in a dissimilar manner. Thus, different parts of A. orientalis revealed variable potential to induce cell death in cancer cells via apoptotic and non-apoptotic pathways, making A. orientalis a valuable plant for the exploration of anticancer bioactive reagents, some of which may be protective for normal cells.

Organic extracts from Cleome droserifolia exhibit effective caspase-dependent anticancer activity

“…None of the other solvents could purify molecules with any significant cytotoxic activity. This observation agrees with our studies with other plant extracts where dichloromethane was the best at isolating the anticancer potential of the plant [52,53]. These observations suggest that the dichloromethane solvent is one of the better organic solvents at extracting anticancer bioactive molecules from medicinal plants with cytotoxic effects against human cancer cells.…”

“…8). We have observed similar effects of two other natural plant products on autophagy when apoptosis was induced by their organic fractions, although the precise pattern of induction of SQSTM1/p62 and LC3 was different with each plant product [52,53]. In fact, this pattern differed even between the organic fraction from leaves (AOD (L)) versus the stems (AOB (S)) from the same plant, Acridocarpus orientalis.…”

“…These subtleties were reflective in the IC 50 values calculated at the 250 μg/ml value 72 h post treatment which revealed that the normal MCF-10A were the most sensitive to CDD-induced killing with an IC 50 value of 57.34 μg/ml, followed by HeLa and MCF-7 cells at 73.23 and 74.63 μg/mL, respectively, while MDA-MB-231 were less sensitive with an IC 50 of 122.8 μg/ml. These values are in the same range as observed for the cell killing potential of two other medicinal plants that we have tested in these cell lines [52,53]. To ensure that the cytotoxicity being observed was not due to any residual organic solvent in the tested fractions, each of the organic solvents by itself was tested on the three cancer cell lines and observed to be non-toxic (data not shown).…”

“…6a and b). Treatment with an essential oil from Boswellia sacra (positive control) that induces potent apoptosis in breast cancer cells [52,53,58] shifted 74% of the cells to the AV(+)/PI(−) quadrant indicative of early apoptosis, and 5.5% of the cells to the AV(+)/PI(+) quadrant, indicative of late apoptosis (Fig. 6c).…”

“…Induction of autophagy is actively being explored as an important cellular pathway activated by anticancer compounds [60][61][62][63]. Our earlier work with two other medicinal plants, Teucrium mascatense and Acridocarpus orientalis has shown that induction of apoptosis by natural products can activate/perturb autophagy as well [52,53]. Therefore, we tested the ability of CDD to induce key proteins of the autophagy pathway, the autophagy receptor, SQSTM1/p62, responsible for recognizing the ubiquitinated cellular cargo targeted for degradation, and the microtubule-associated protein 1 light chain 3 expressed in the cytoplasm (LC3-I) or its cleaved form (LC3-II) that is recruited to the autophagosome via lipidation upon autophagy activation [59].…”