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Multidrug resistance (MDR) represents an obstacle in anti-cancer therapy. MDR is caused by multiple mechanisms, involving ATP-binding cassette (ABC) transporters such as P-glycoprotein (P-gp), which reduces intracellular drug levels to sub-therapeutic concentrations. Therefore, sensitizing agents retaining effectiveness against apoptosis- or drug-resistant cancers are desired for the treatment of MDR cancers. The sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) pump is an emerging target to overcome MDR, because of its continuous expression and because the calcium transport function is crucial to the survival of tumor cells. Previous studies showed that SERCA inhibitors exhibit anti-cancer effects in Bax-Bak-deficient, apoptosis-resistant and MDR cancers, whereas specific P-gp inhibitors reverse the MDR phenotype of cancer cells by blocking efflux of chemotherapeutic agents. Here, we unraveled SERCA and P-gp as double targets of the triterpenoid, celastrol to reverse MDR. Celastrol inhibited both SERCA and P-gp to stimulate calcium-mediated autophagy and ATP depletion, thereby induced collateral sensitivity in MDR cancer cells. In vivo studies further confirmed that celastrol suppressed tumor growth and metastasis by SERCA-mediated calcium mobilization. To the best of our knowledge, our findings demonstrate collateral sensitivity in MDR cancer cells by simultaneous inhibition of SERCA and P-gp for the first time.

BACKGROUND: We have investigated the potential anticancer effects of karanjin, a principal furanoflavonol constituent of the Chinese medicine Fordia cauliflora, using cytotoxic assay, cell cycle arrest, and induction of apoptosis in three human cancer cell lines (A549, HepG2 and HL-60 cells). RESULTS: MTT cytotoxic assay showed that karanjin could inhibit the proliferation and viability of all three cancer cells. The induction of cell cycle arrest was observed via a PI (propidium iodide)/RNase Staining Buffer detection kit and analyzed by flow cytometry: karanjin could dose-dependently induce cell cycle arrest at G2/M phase in the three cell lines. Cell apoptosis was assessed by Annexin V-FITC/PI staining: all three cancer cells treated with karanjin exhibited significantly increased apoptotic rates, especially in the percentage of late apoptosis cells. CONCLUSION: Karanjin can induce cancer cell death through cell cycle arrest and enhance apoptosis. This compound may be effective clinically for cancer pharmacotherapy.

5-(3'-Hydroxyphenyl)pentanoic acid (1) and 5-(3'-methoxyphenyl)pentanoic acid (2) occurring in the roots of Athyrium yokoscense showed transport activity to alkaline and alkaline earth metal ions and heavy divalent metal ions.

Background. Dendrobium officinale(DO) Kimura et Migo is a precious Chinese herb that is considered beneficial for health due to its antioxidant and antidiabetes properties, and so on. In this research, we try to determine the preventive effect of DO on the early complications of STZ-induced diabetic rats.Methods. Type 1 diabetic rats were produced with a single intraperitoneal injection of STZ (50 mg/kg). DO (1 g/kg/day) was then orally administered for 5 weeks. Blood glucose, TC, TG, BUN, CREA, and GSH-PX levels were determined, and electroretinographic activity and hypoalgesia were investigated. Pathological sections of the eyes, hearts, aortas, kidneys, and livers were analyzed.Results. Treatment with DO significantly attenuated the serum levels of TC, TG, BUN, and CREA, markedly increased the amplitudes of ERG a- and b-waves and Ops, and reduced the hypoalgesia and histopathological changes of vital organs induced by hyperglycemia. The protective effect of DO in diabetic rats may be associated with its antioxidant activity, as evidenced by the marked increase in the serum level of glutathione peroxidase. However, DO had no significant effect on blood glucose levels and bodyweight of diabetic rats.Conclusions. DO supplementation is an effective treatment to prevent STZ-induced diabetic complications.

5-(3-Hydroxyphenyl)pentanoic acid (1) and 5-(3-methoxyphenyl)pentanoic acid (2) were isolated from the roots of Athyrium yokoscense as natural products. The biosynthetic pathway of 1 and 2 can be explained in terms of direct m-hydroxylation of benzoic acid.

A novel phytoecdysone, 24-epi-pterosterone, was isolated from a water extract of the roots of Athyrium yokoscense and the structure was determined to be (20R,22R,24R)-2β,3β,14α,20,22,24-hexahydroxy-5β-cholest-7-en-6-one by a combination of spectroscopic methods and single-crystal X-ray analysis. 24-Epi-pterosterone is the first example of an ecdysteroid possessing a 24R-hydroxyl group.

A novel phytoecdysone, 24-epi-pterosterone, was isolated from a water extract of the roots of Athyrium yokoscense and the structure was determined to be (20R,22R,24R)-2β,3β,14α,20,22,24-hexahydroxy-5β-cholest-7-en-6-one by a combination of spectroscopic methods and single-crystal X-ray analysis. 24-Epi-pterosterone is the first example of an ecdysteroid possessing a 24R-hydroxyl group.