Effect of Methoxsalen on Ca^(2+) Homeostasis and Viability in Human Osteosarcoma Cells

Abstract

Methoxsalen is a natural compound found in many seed plants. The effect of methoxsalen on Ca²⁺- related physiology in human osteosarcoma is unclear. This study investigated the effect of methoxsalen on cytosolic free Ca²⁺ concentrations ([Ca²⁺]i) in MG63 human osteosarcoma cells. Methoxsalen induced [Ca²⁺]i rises concentration-dependently. Methoxsalen-induced Ca²⁺ entry was confirmed by Mn²⁺-induced quench of fura-2 fluorescence. This Ca²⁺ entry was suppressed by nifedipine, econazole, and SKF96365. In Ca²⁺-free medium, incubation with the endoplasmic reticulum Ca²⁺ pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) inhibited methoxsalen-evoked [Ca²⁺]i rises by 96%. In contrast, incubation with methoxsalen abolished BHQ-evoked [Ca²⁺]i rises. Inhibition of phospholipase C (PLC) with U73122 abolished methoxsalen-induced [Ca²⁺]i rises. Methoxsalen was cytotoxic at 300-700 μM in a concentration-dependent fashion. Chelating cytosolic Ca²⁺ with 1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid/acetoxymethyl ester (BAPTA/AM) did not prevent methoxsalen-induced cytotoxicity. Collectively, our data suggest that in MG63 cells, methoxsalen induced [Ca²⁺]i rises by evoking PLC-dependent Ca²⁺ release from the endoplasmic reticulum, and Ca²⁺ entry via store-operated Ca²⁺ entry. Methoxsalen also induced Ca²⁺- disassociated cell death.

TRPM7 promotes the epithelial–mesenchymal transition in ovarian cancer through the calcium-related PI3K / AKT oncogenic signaling

“…We found that TRPM7 silencing dramatically reduced the levels of TRPM7 expression and the levels of [Ca 2+ ]i in ovarian cancer cells. Similarly, treatment with BAPTA-AM to inhibit the calcium channel also reduced the levels of [Ca 2+ ]i, consistent with previous observations [43, 46, 47] and attenuated the IGF-induced migration, invasion and wound healing in ovarian cancer cells. Accordingly, such data indicate that both the calcium signaling and the PI3K/AKT pathway positively promote the migration and invasion of ovarian cancer cells [48, 49].…”

Methoxsalen and Bergapten Prevent Diabetes-Induced Osteoporosis by the Suppression of Osteoclastogenic Gene Expression in Mice

“…However, the effects of BP on hyperglycemia-induced osteoporosis are not yet understood. MTS is also a natural photoactive compound found in many plant seeds [18] and a structural isomer of BP, but its anti-osteoporotic function has been relatively less studied compared with BP. We would like to develop BP or MTS as a food ingredient or a food supplement for preventing DM-related osteoporosis.…”

β Lapachone blocks the cell cycle and induces apoptosis in canine osteosarcoma cells

“…Similarly, Cinegaglia et al (2013) described that the human osteosarcoma cells (HOS) were sensitive to the dose-dependent cytotoxic effect at concentrations between 50µg to 100µg of propolis, a product collected from exudates of plants mixed with wax and saliva enzymes of bees. Also, the methoxsalen, a natural compound found in seeds of several plants, was cytotoxic to osteosarcoma cells MG63, in the dosages between 300μm and 500μm (Lu et al 2017). On the other hand, carboplatin did not present cytotoxic activity in OSC cells in the assays performed by Stein et al (2011) and in HOS cells in the study by Robson et al (2007).…”