Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran.
Department of Biology, College of Science for Women, Babylon University, Hillah, Iraq.
J Cell Physiol. 2019 Nov;234(11):19271-19279. doi: 10.1002/jcp.28563. Epub 2019 Apr 16.
l-Asparaginases hydrolyzing plasma l-asparagine and l-glutamine has attracted tremendous attention in recent years owing to remarkable anticancer properties. This enzyme is efficiently used for acute lymphoblastic leukemia (ALL) and lymphosarcoma and emerged against ALL in children, neoplasia, and some other malignancies. Cancer cells reduce the expression of l-asparaginase leading to their elimination. The l-asparaginase anticancerous application approach has made incredible breakthrough in the field of modern oncology through depletion of plasma l-asparagine to inhibit the cancer cells growth; particularly among children. High level of l-asparaginase enzyme production by Escherichia coli, Erwinia species, Streptomyces, and Bacillus subtilis species is highly desirable as bacterial alternative enzyme sources for anticancer therapy. Thermal or harsh conditions stability of those from the two latter bacterial species is considerable. Some enzymes from marine bacteria have conferred stability in adverse conditions being more advantageous in cancer therapy. Several side effects exerted by l-asparaginases such as hypersensitivity should be hindered or decreased through alternative therapies or use of immune-suppressor drugs. The l-asparaginase from Erwinia species has displayed remarkable traits in children with this regard. Noticeably, Erwinia chrysanthemi l-asparaginase exhibited negligible glutaminase activity representing a promising efficiency mitigating related side effects. Application of software such as RSM would optimize conditions for higher levels of enzyme production. Additionally, genetic recombination of the encoding gene would indisputably help improving enzyme traits. Furthermore, the possibility of anticancer combination therapy using two or more l-asparaginases from various sources is plausible in future studies to achieve better therapeutic outcomes with lower side effects.
近年来，能够水解血浆中 l-天冬酰胺和 l-谷氨酰胺的 l-天冬酰胺酶因其显著的抗癌特性而引起了极大的关注。这种酶被有效地用于治疗急性淋巴细胞白血病（ALL）和淋巴肉瘤，并在儿童、肿瘤和其他一些恶性肿瘤中对抗 ALL。癌细胞会降低 l-天冬酰胺酶的表达，从而导致其被消除。通过消耗血浆中天冬酰胺来抑制癌细胞生长，l-天冬酰胺酶的抗癌应用方法在现代肿瘤学领域取得了令人难以置信的突破；特别是在儿童中。大肠杆菌、欧文氏菌、链霉菌和枯草芽孢杆菌等细菌产生高水平的 l-天冬酰胺酶，作为抗癌治疗的替代酶源，这是非常理想的。后两种细菌来源的酶在热或苛刻条件下具有相当的稳定性。一些来自海洋细菌的酶在不利条件下具有稳定性，在癌症治疗中更具优势。l-天冬酰胺酶会产生一些副作用，如过敏反应，应通过替代疗法或使用免疫抑制剂来抑制或减少这些副作用。在这方面，来自欧文氏菌的 l-天冬酰胺酶表现出了显著的特性。值得注意的是，欧文氏菌 l-天冬酰胺酶的谷氨酰胺酶活性可忽略不计，这代表了一种有前途的效率，可以减轻相关的副作用。使用 RSM 等软件可以优化条件，以提高酶的产量。此外，对编码基因进行遗传重组无疑有助于改善酶的特性。此外，在未来的研究中，使用来自不同来源的两种或更多种 l-天冬酰胺酶进行抗癌联合治疗的可能性是合理的，以达到更好的治疗效果和更低的副作用。
