Antimalarial drugs from different classes have demonstrated anticancer effects in different types of cancer cells, but their complete mode of action in cancer remains unknown. Recently, several studies reported the important role of palmitoyl-protein thioesterase 1 (PPT1), a lysosomal enzyme, as the molecular target of chloroquine and its derivates in cancer. It was also found that PPT1 is overexpressed in different types of cancer, such as breast, colon, etc. Our group has found a synergistic interaction between antimalarial drugs, such as mefloquine, artesunate and chloroquine and antineoplastic drugs in breast cancer cells, but the mechanism of action was not determined. Here, we describe the importance of autophagy and lysosomal inhibitors in tumorigenesis and hypothesize that other antimalarial agents besides chloroquine could also interact with PPT1 and inhibit the mechanistic target of rapamycin (mTOR) signalling, an important pathway in cancer progression. We believe that PPT1 inhibition results in changes in the lysosomal metabolism that result in less accumulation of antineoplastic drugs in lysosomes, which increases the bioavailability of the antineoplastic agents. Taken together, these mechanisms help to explain the synergism of antimalarial and antineoplastic agents in cancer cells.

中文翻译：

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抗疟药和抗肿瘤药物如何在联合治疗中相互作用：对 PPT1 酶作用的看法。

不同类别的抗疟疾药物已在不同类型的癌细胞中显示出抗癌作用，但它们在癌症中的完整作用方式仍不清楚。最近，一些研究报道了棕榈酰蛋白硫酯酶 1 (PPT1)（一种溶酶体酶）作为氯喹及其衍生物在癌症中的分子靶标的重要作用。还发现PPT1在不同类型的癌症中过度表达，如乳腺癌、结肠癌等。本课题组发现甲氟喹、青蒿琥酯和氯喹等抗疟药与抗肿瘤药在乳腺癌细胞中存在协同作用，但作用机制未确定。这里，我们描述了自噬和溶酶体抑制剂在肿瘤发生中的重要性，并假设除氯喹之外的其他抗疟药也可以与 PPT1 相互作用并抑制雷帕霉素 (mTOR) 信号传导的机制靶标，这是癌症进展的重要途径。我们认为 PPT1 抑制会导致溶酶体代谢发生变化，从而导致抗肿瘤药物在溶酶体中的积累减少，从而提高抗肿瘤药物的生物利用度。总之，这些机制有助于解释抗疟药和抗肿瘤药在癌细胞中的协同作用。我们认为 PPT1 抑制会导致溶酶体代谢发生变化，从而导致抗肿瘤药物在溶酶体中的积累减少，从而提高抗肿瘤药物的生物利用度。总之，这些机制有助于解释抗疟药和抗肿瘤药在癌细胞中的协同作用。我们认为 PPT1 抑制会导致溶酶体代谢发生变化，从而导致抗肿瘤药物在溶酶体中的积累减少，从而提高抗肿瘤药物的生物利用度。总之，这些机制有助于解释抗疟药和抗肿瘤药在癌细胞中的协同作用。